Positive results from the phase 3 trial of AD04 show a 79% reduction in heavy drinking.
Successful results were announced from the ONWARD trial, a phase 3 clinical study evaluating the efficacy, safety, and tolerability of AD04 in patients with alcohol use disorder (AUD) and selected polymorphisms in the serotonin transporter and receptor genes. AD04 achieved statistically significant mean reduction in heavy drinking days among the prespecified group of “heavy drinkers,” and showed a better safety and tolerability profile compared with placebo. Adial Pharmaceuticals conducted the study.
Professor Hannu E.R. Alho, Emeritus Professor of Addiction Medicine at the University of Helsinki and Principal Investigator for the ONWARD trial, said, “These study results may provide hope to millions of people worldwide suffering from AUD, as well to the families of those impacted by this devastating disease. Among heavy drinkers, which make up the majority of my practice, we saw a clear and statistically significant reduction in heavy drinking days for those patients receiving AD04 versus placebo. These results demonstrate the effectiveness of AD04 for heavy drinker AUD patients.”1
Participants who received AD04 achieved a statistically significant reduction from baseline at month 6 in heavy drinking days for the prespecified patient group of heavy drinkers who averaged less than 10 drinks per drinking day at baseline; p=0.03. A similar trend was seen in the combined month 5 and 6 analysis in the reduction from baseline (p =0.07). In the last month of the trial, patients who were heavy drinkers and received AD04 had a mean reduction of approximately 79% in heavy drinking compared with baseline.
In addition, AD04 resulted in a reduction from baseline at month 6 compared with placebo in heavy drinking days for the combined trial population of heavy and very heavy drinkers (p=NS). At conclusion of the trial, compared with placebo, AD04 in the heavy drinking group resulted in an overall significant difference in the severity of the AUD diagnosis (p=0.04) under the DSM-5. For the group of those who no longer met AUD criteria ( less than 2 symptoms), the comparisons were 27.4% versus 14.9% (ie, an 84% decrease), of AD04 and placebo, respectively. These data underscore the clinical relevance of the findings that patients who are heavy drinkers who receive AD04 appear more likely to recover from the disease by the end of the treatment regimen.
“It has been my life mission to develop new therapies that provide patients with a means to either curb the impulse to drink, or abstain from alcohol entirely,” said Bankole Johnson, MD, Chief Medical Officer of Adial. “AUD accounts for more than 5% of deaths worldwide and is the number one indicator of death for men and women ages 15 to 49, the prime of their lives. The ONWARD study reinforces that AUD is a multi-factorial disease with a diverse set of neurobiological components. The ONWARD data appears to support our earlier findings that AD04 is a genetically targeted medical treatment addressing the biology of AUD. We believe our finding that AD04 appears as safe as placebo should increase its acceptability in general practice and eventually lead to widespread adoption of AD04 for treatment of AUD.”1
The safety and tolerability profile was similar to placebo and consistent with the phase 2b trial. Adverse effects reported with a frequency of 5% or more of patients in either group were headache (11% on placebo, 12% on AD04), insomnia (3% on placebo, 7% on AD04), blood magnesium decreased (5% on placebo, 6% on AD04), and fatigue (3% on placebo, 6% on AD04). All were reported as mild to moderate.
William Stilley, Chief Executive Officer of Adial, commenting on the trial results, said, “Alcohol use disorder is an unmet medical need that affects tens of millions of people each year, and, based on the strength of these ONWARD results in heavy drinking patients that have the target genetics, and the fact that AD04 demonstrated an exceptional safety profile, and was well-tolerated during the trial, we intend to advance AD04. We will work with regulatory authorities in Europe and the US to achieve this goal.”1
1. Adial Pharmaceuticals announces topline results for Onward™ phase 3 trial for AD04 in patients with alcohol use disorder. Adial. July 20, 2022. https://www.adial.com/adial-pharmaceuticals-announces-topline-results-for-onward-phase-3-trial-for-ad04-in-patients-with-alcohol-use-disorder/